In view of the continuing high number of deaths each year resulting from cancer, a continuing need exists to identify effective and less toxic therapeutic regimens for use in anticancer treatment.
For a variety of epithelial cell cancers, or carcinomas, treatment with an epithelial growth factor (EGF) pathway inhibitor has been proposed or demonstrated. Trastuzumab (Herceptin®), a humanized monoclonal that specifically targets the human epidermal growth factor 2 (HER2) receptor, inhibits the EGF signaling pathway associated with HER2. The anti-HER2 antibody may be indicated particularly in the treatment of cancers, such as breast and ovarian cancers, characterized by HER2 overexpression in carcinoma cells.
Cetuximab (Erbitux®) is a chimeric monoclonal antibody that likewise acts as an EGF pathway inhibitors by binding to epidermal growth factor receptor 1 (EGFR, ErbB-1 or HER1), and may be indicated, for example, for the treatment of metastatic colorectal cancer and head and neck cancer.
A number of small molecule anti-cancer agents that target the EGF pathway have also been proposed in anti-cancer treatment. Erlotinib (Tarceva®) and gefitinib (Iressa®) specifically target the tyrosine kinase activity of EGFR, which may be highly expressed and occasionally mutated in various forms of cancer. The drug molecules bind in a reversible fashion to the adenosine triphosphate (ATP) binding site of the receptor, effectively blocking autophosphorylation of EGFR homodimers, and thus blocking the signal cascade to the nucleus. Both compounds have shown a survival benefit in the treatment of lung cancer in phase III trials, and have been approved for the treatment of locally advanced or metastatic non small cell lung cancer.
EGF pathway inhibitors are but one class of a large number of anti-cancer agents that may be selected for treating cancer. In addition, any selected class of anti-cancer agent may be tested with one or more other anti-cancer agents in a combination treatment, to determine if the two or more agents together are capable of producing an additive therapeutic effect, or other significant advantage, such as a reduction in undesired side effects, due to a reduced dose of the more toxic component, and/or a reduction in the development of drug-resistance in the cancer being treated.
It would be desirable to provide a combined-drug cancer therapy for the treatment carcinomas in which both drug components are relatively specific against cancer cells, each acting through a mechanism that involves specific binding of the drug compound to a cellular component associated preferentially with the cancer cells.